Protective effect of hydroxysafflor yellow A on renal ischemia‑-reperfusion injury by targeting the Akt‑Nrf2 axis in mice.

Abstract

Ischemic/reperfusion (I/R) injury is the primary cause of acute kidney injury (AKI). Hydroxysafflor yellow A (HSYA), a natural compound isolated from Carthamus tinctorius L., has been found to possess anti-inflammatory and antioxidant properties. However, the protective effects and potential mechanism of HSYA on I/R-induced AKI remains unclear. In the present study, the in vitro hypoxia/reoxygenation (H/R) and in vivo renal I/R models were employed to investigate the renal protective effects and molecular mechanisms of HSYA on I/R-induced AKI. The present results indicated that HSYA pretreatment significantly ameliorated renal damage and dysfunction in the I/R injury mice via enhancing the antioxidant capacity and suppressing the oxidative stress injury, inflammatory response, and apoptosis. Mechanistic studies showed that HSYA could upregulate Akt/GSK-3β/Fyn-Nrf2 axis-mediated antioxidant gene expression both in vitro and in vivo. Moreover, HSYA-mediated improvement in antioxidant, anti-inflammatory, and anti-apoptotic effects in H/R-treated HK-2 cells was abrogated by Akt inhibitor LY294002 supplementation. In summary, the present results demonstrated that HSYA attenuated kidney oxidative stress, inflammation response, and apoptosis induced by I/R, at least in part, via activating the Akt/GSK-3β/Fyn-Nrf2 axis pathway. These findings provided evidence that HSYA may be applied as a potential therapeutic agent in the treatment of I/R induced AKI.

• Authors: Yueming Wang, Kaiyue Han, Zile Li, Xiaoxuan Tang, Chen Wang, Yaxuan Zhao, Hengchao Zhang, Ziran Geng, Jie Kong, Xiying Luan, Yanlian Xiong
• Journal: Experimental and therapeutic medicine (Exp Ther Med) Vol. 24 Issue 6 Pg. 741 (Dec 2022) ISSN: 1792-1015 [Electronic] Greece
• PMID: 36478883 (Publication Type: Journal Article)
• Copyright: Copyright: © Wang et al.